Immunotherapy of patients with metastatic malignant melanoma using tumor infiltrating lymphocytes and interleukin-2 has resulted in significant clinical regressions. We have previously identified in vitro functions of these lymphocytes which have correlated with subsequent clinical response. Our present studies are focused on the identification of lymphocytes infiltrating breast and ovarian carcinomas that have specific antitumor reactivity. Our goal is to translate these findings into therapies for patients with these diseases. 1. Screening of breast cancer infiltrating lymphocytes. We initially discovered that lymphocytes derived from 3 of 11 breast carcinomas specifically secreted GM-CSF, TNF-alpha, and IFN-gamma in response to autologous tumor stimulation. Subsequently we have screened lymphocyte cultures from 34 breast cancer patients and have identified 3 that specifically secrete cytokines in an MHC class II restricted fashion. In parallel we are attempting to grow breast cancers in SCID mice with approximately a 50% success rate. We are also attempting to develop antigen presenting cells that can present tumor antigens to autologous lymphocytes which are specific cytokine secretors. If we are successful in generating these reagents the plan is to use them in identification of breast tumor antigens. These findings would have great potential value in the developments of vaccines and other immunotherapies. 2. Screening of ovarian cancer infiltrating lymphocytes. Lymphocytes derived from malignant ascites or from solid tumor metastases have been cultured. These lymphocytes are being characterized for phenotype, cytotoxicity, and ability to secrete cytokines in response to autologous tumor stimulation. If tumor specific lymphocytes can be identified, the plan is to characterize the antigens which they are recognizing and eventually use these defined antigens to create vaccines.